PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway

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Reyhani, VahidUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab (author)

PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway

Article/chapterEnglish2017

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2017-08-21
Springer Science and Business Media LLC,2017
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LIBRIS-ID:oai:DiVA.org:uu-331647
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-331647URI
https://doi.org/10.1038/s41598-017-08411-1DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3'-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.

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Tsioumpekou, MariaUppsala universitet,Ludwiginstitutet för cancerforskning,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)marts122 (author)
van Wieringen, Tijs,1979-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)tiwie845 (author)
Rask, LarsUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)lra10568 (author)
Lennartsson, JohanUppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)johalenn (author)
Rubin, KristoferUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)krisrubi (author)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

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